Critical Roles of Oxidative Signals in Age-Related Decline of Cerebellar Synaptic Plasticity

  • Sho Kakizawa
  • Nozomu MoriEmail author


A strong correlation between increasing age and the accumulation of oxidative modifications of functional molecules, such as proteins and lipids, has been observed in biological systems, including the central nervous system. Thus, oxidative signals, especially reactive oxygen species (ROS), are thought to be primary factors affecting age-related decline in brain functions. However, the molecular mechanism of the inhibitory action of oxidative signals is not yet fully understood. In this review article, we introduce our novel hypothesis on the molecular mechanism of aging in the nervous system: oxidative signals impair neuronal function through the inhibition of protein S-nitrosylation by nitric oxide (NO). This idea is based on the fact that the thiol group in cysteine residues is the common target of NO and oxidative signals. Actually, S-nitrosylation-dependent synaptic plasticity in the cerebellar cortex as well as NO-induced S-nitrosylation of cerebellar proteins are abolished by ROS treatment and aging. Furthermore, the functions of some proteins involved in synaptic plasticity, such as NSF, stargazin and ryanodine receptor 1, are demonstrated to be regulated in dependent on S-nitrosylation. Taken together, these studies open a new avenue in the study of the molecular mechanism of brain aging.


Aging Brain S-nitrosylation Oxidative stress Posttetanic potentiation Long term potentiation Cerebellum Purkinje cell Parallel fiber 


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Copyright information

© Springer Japan 2015

Authors and Affiliations

  1. 1.Department of Biological Chemistry, Graduate School of Pharmaceutical SciencesKyoto UniversityKyotoJapan
  2. 2.Department of Anatomy and Neurobiology, Graduate School of Biomedical SciencesNagasaki UniversityNagasakiJapan

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